Our investigative efforts will continue to be directed into two major areas. I. Using clearance, metabolic balance and micropuncture techniques, we will study the factors which regulate renal excretion of sodium, calcium and phosphate in experimental animals. These studies will evaluate interrelationships between ions, sodium-independent phosphate transport and various hormonal and metabolic factors. In addition using a recently developed genetic strain of mice, we will investigate the pathophysiology of hereditary hypophosphatemic rickets. Continuing our investigation of the effects of phosphate depletion, acid base homeostasis will be studied. We propose to begin an investigation of the pathogenesis and treatment of nephrocalcinosis using this model. II. Electrolyte disturbances in man will continue to be a major focus and include studies of patients with abnormalities of phosphate transport (vitamin D resistant rickets) and calcium transport (nephrolithiasis and hypercalciuria). We will continue our studies with uric acid transport to evaluate mechanisms of hypouricemia in patients with a wide variety of tubular disorders. In addition, as part of our continuing study of mechanisms of hyponatremia, the renal adaptation to chronic alterations in extracellular fluid volume will be studied in man. BIBLIOGRAPHIC REFERENCES: DeFronzo, R.A., Goldberg, M. and Agus, Z.S. Normal diluting capacity in hyponatremic patients: reset osmostat or a variant of SIADH. Ann. Int. Med. 84: 538-542, 1976. Goldfarb, S., Cox, M., Singer, I. and Goldberg, M. Acute hyperkalemia induced by hyperglycemia: hormonal mechanisms. Ann. Int. Med. 84: 426-432, 1976, in press.